This invention relates generally to invasive medical devices and more particularly to flexible instruments designed to enter the living tissue to make measurements, deliver drugs and/or selectively sample or alter the chemical environment or analysis inside or outside of the body, and more particularly to a microdialysis probe suitable for connection to another primary probe to be extended through a common opening into the body of a living being.
Biological fluids contained in the interstitial space of tissues are often sampled for research and diagnostic purposes. Also, it is often required that the chemical composition of the interstitial space be altered via pharmacological or physiological means. Microdialysis, which employs an invasive semipermeable membrane at the end of two open ducts makes it possible to selectively sample or deliver low molecular weight substances to the interstitial space.
In U.S. Pat. No. 4,694,832 (Ungerstedt) there is disclosed a method for building a dialysis probe intended for insertion in biological tissues, for example brain tissue, containing a dialysis membrane and ducts for flow of the perfusion fluid over the membrane, and containing supports for the membrane and ducts. The probe described requires the existence of a support structure for the ducts and membrane, and thus requires its own entry port and produces its own track or laceration of the tissue as it descends into the tissue being analyzed.
In U.S. Pat. No. 5,191,900 (Mishra) there is disclosed an alternate method of fabrication of a dialysis probe, which makes use of a U-shaped loop that uses an internal, biologically inert wire combined with internal hydrostatic pressure to support the dialysis membrane and ducts. Alternative side-by-side and concentric probe configurations are also described, which exploit similar principles for support of the dialysis membrane and ducts. The Mishra '900 patent thus describes a dialysis probe which also requires its own entry port and/or the making of a separate track or laceration to enter the tissue which is to be analyzed.
As will be appreciated by those skilled in the art the use of the probes of the above two patents require the dedication of an entry port and/or the creation of a track or laceration for the dialysis probe itself. Thus, if either of these probes is to be used with another probe, i.e., a primary probe of a different type, e.g., an electrical probe, two bores will have to be provided in patient's skull, one for each probe. These limitations may be minor hindrances in some cases, e.g., blood sampling, or may be prohibitive in other cases, e.g., brain surgery, since the brain is not capable of regenerating injured or destroyed tissue. Moreover, these limitations apply whether the probe is to be used for analytical/diagnostic purposes or for therapeutic purposes. Thus, while the microdialysis probes of the above mentioned patents are suitable for their intended purposes they leave something to be desired from the standpoint of functionality.
Other probes are disclosed in U.S. Pat. Nos. 4,903,707 (Kunte), 4,931,049 (Klimas) and 5,106,365 (Hernandez).
Since the present commercially available microdialysis probes use a dedicated port of entry, they suffer from another disadvantage in order to be useful for clinical purposes; they can only be used in their miniature versions which are intended to be used primarily in rodents. The maximum surface areas and flow rates they allow coupled with the present analytical sensitivities limit their use for sampling only; that too with a poor temporal resolution. The existing microdialysis probes allow very low flow rates (0.5 to 5 ul per minute) in order to achieve reasonably high (5% to 30%) efficiency of capture of tissue analytes. This low rate is required because otherwise, there is a non-negligible depletion from the small amount of tissue surrounding the dialysis probe. Since preceding designs of dialysis probes have surface areas of about 3.8 mm.sup.2, there is a small amount of tissue surface to cope with the flow volume. In the existing devices, typically, dialysates are collected at a flow rate of 0.5-5 ul/min for 10-60 min and then analyzed. The low collected quantities of these chemical are insufficient for any on-line analysis in real time for most interstitial chemicals. Constructing the prior art probes in relatively larger dimensions would eliminate some of these problems but the most common application of microdialysis being in brain tissue, having a laceration of larger magnitude in the brain to achieve these goals represents a major disadvantage, at least until there is a demonstrated evidence of any improvement in patient outcome associated with the use of these probes.
It should be noted that there is a suggestion in the prior art to the use of a microdialysis probe joined with another component for performing microdialysis and another function via a common entrance port. For example, in an article entitled Modified Microdialysis Probe For Sampling Extracellular Fluid And Administering Drugs In Vivo, by G. Yadid, K Pacak, I. J. Kpoin, and D. S. Goldstein, appearing in American Journal Of Physiology, Volume 265, 1993, pages R1205-R1211, there is disclosed a microdialysis probe having a cannula glued to its external surface to enable the administration of a pharmacological agent, glycine, through the cannula to evaluate the behavioral effect thereof on the subject, e.g., conscious rats.
In an article entitled Combined Intracerebral Microdialysis And Electrophysiological Recording: Methodology and Applications, by T. P. Obrenovitch, D. A. Richards, G. S. Sarna, and L. Symon, in the Journal Of Neuroscience Methods, Volume 47, pages 139-145, 1993, there is disclosed a microdialysis probe including in its housing a chlorided silver wire electrode for electrophysiological recording. That probe also only needs a single access port. The electrophysiological measurements, e.g., EEG and DC potentials, are obtained by the device by measuring the potential between its chlorided silver electrode and a remotely placed Ag/AgCl reference electrode.
As should be appreciated by those skilled in the art the microdialysis probes disclosed in the two above mentioned articles are integrated devices, that is the probe and the other component, be it a cannula or an electrode, are permanently secured to the probe and form a part of the probe. Hence, such devices are of limited utility and cannot be used for a wide variety of applications. Moreover, the combined structures are somewhat bulky and could result in excessive damage to adjacent tissue upon the introduction thereof into the being's body, e.g., the brain. Thus, a need still exists for a combination microdialysis probe and a primary probe of any type, and which combination will not result in excessive damage to adjacent tissue.